W/O/W composite emulsion

ABSTRACT

A W/O/W type composite emulsion, wherein a W/O type emulsion containing water, an oil ingredient and a lipophilic emulsifier each in a proportion expressed in term of mass ratio falling within a range enclosed with bold lines in FIG.  1  is dispersed in an external aqueous phase with a water-soluble macromolecule blended therein has a sufficient stability, and permits preserving a percent inclusion of medical substances included in an internal aqueous phase of the W/O/W type composite emulsion at a high level. 
     Because of the characteristics, it is now possible to blend in a liquid formulation medical substances having an unfavorable taste or unstable medical substances which have to date hardly been included in liquid formulations with low viscosity, so that the W/O/W type composite emulsion can be utilized for liquid formulations including a liquid formulation for internal application, injections, etc.

FIELD OF THE INVENTION

The present invention relates to a W/O/W type composite emulsion.

PRIOR ART

Liquid formulations are a type of formulation well adapted to use byordinary people. For instance, liquid formulations for internalapplication can easily be administered to the aged people as well as toinfants and children, who have low swallowing capability, so that liquidformulations are widely used as a medicine or a functional food.

However, when medical substances having unpleasant taste such asbitterness are blended in a liquid formulation for internal application,the taste of the medical substances is directly felt by the user, sothat the taste of the liquid formulation itself becomesdisadvantageously unpleasant. Further, in a liquid formulation, theadded medical substances easily react with each other, and therefore ithas been difficult to blend medical substances each having highreactivity in a liquid formulation.

To prevent the taste of a liquid formulation from becoming unpleasant,the method of masking the unpleasant taste of a liquid formulation byblending various types of taste-improving agents in the liquidformulation is often employed. In this method of masking the unpleasanttaste by blending taste-improving agents therein, however, there areseveral restrictions such as the limited quantity of medical substanceswhich can be blended in the liquid formulation.

As a method of blending medical substances in a liquid formulation inthe stable state, the method of emulsifying the liquid formulation isalso known. As water-soluble medical substances and fat-soluble medicalsubstances can be blended together in an emulsion, many reports havebeen made for application of emulsions, for instance, in medicines.However, for conventional O/W type emulsions, it is difficult to preventthe medical substances contained therein from reacting with each other.

W/O/W type composite emulsions are advantageous in that they permitblending of water-soluble medical medicines, which are generally notadapted to blending due to the stability and taste, in an internalaqueous phase. They are also advantageous in that they permitpreparation of an administrative preparation in which such medicalsubstances that easily react to each other and can hardly be blendedtogether are incorporated in combination into a preparation, since themedical substances can be isolated from each other by including some ofthe medical substances in an internal aqueous phase and the others in anexternal aqueous phase. As the W/O/W type composite emulsions aregenerally low in their stability, they are used in creamy preparationswith high viscosity in which the stability is relatively preserved;however, there has been no report on use of W/O/W composite emulsions insuch a preparation that is used as a liquid formulation for internalapplication with a viscosity of 150 mPa·s or below.

There has generally been known for emulsions that, the smaller theparticle diameter of emulsions, the higher the dispersion stabilitythereof in a liquid formulation is. When the particle diameter of W/O/Wtype composite emulsion is made smaller, however, medical substancesflow out from the internal aqueous phase, which disadvantageously makesthe percent inclusion (a relative quantity of medical substancesincluded in the internal aqueous phase) smaller. Therefore, in the rangeof the particle diameter from 20 to 2000 nm in which the dispersionstability in a liquid formulation can be relatively well preserved, ithas been difficult to produce the W/O/W type composite emulsion at ahigh percent inclusion.

Further the utility value of the W/O/W type composite emulsion becomeshigher as the quantity of medical substances which can be included inone particle of the emulsion is larger. However, when the quantity ofmedical substances included in one particle of emulsion becomes larger,the percent inclusion of medical substances generally becomes lower.

The percent inclusion of medical substances into emulsion can bedetermined as satisfactory when a value (B/Log₁₀C) obtained by dividingthe percent inclusion (%) of medical substances included in the internalaqueous solution of the W/O/W type composite emulsion by a commonlogarithm of the average particle diameter of the W/O/W type compositeemulsion is 27 or more. Unfortunately, there has been no techniqueallowing for production of emulsions having such low viscosity of 150mPa·s or below that allows their use as a liquid formulation and at thesame time meeting the requirements as described above.

As the conventional technique for production of W/O/W type compositeemulsions, JP 4-100536 A discloses, for instance, technique forproduction of W/O/W type composite emulsions by usingpolyglycerin-condensated ricinoleic acid ester, a lipophilic emulsifier.However, the resulting emulsion cannot be satisfactorily applied topractical use, because it has an undesirably large particle diameter andundesirably low dispersion stability.

As the technique for obtaining a W/O/W type composite emulsion having aminute particle diameter, JP 4-99716 A describes a technique forproducing an injection, but the injection produced by the techniquecannot be used as a liquid formulation for internal application becauseof the unfavorable taste of the emulsifier.

Although W/O/W or S/O/W type emulsions are disclosed, for instance, inJP 3-127952 A, JP 10-158152 A, JP 10-203962 A, JP 11-188256 A, JP11-240840 A, all the emulsions provided therein have an undesirablylarge particle diameter.

DISCLOSURE OF THE INVENTION

The inventors of the present invention made an extensive study with anobjective to obtain a W/O/W type composite emulsion which has asufficient stability even in the fine particle state and which canpreserve the percent inclusion of medical substances included in theinternal aqueous phase thereof at a high level. As a result, they havefound that producing a W/O type emulsion by blending water, an oilingredient and a lipophilic emulsifier each with a specific blend ratiodifferent from that in the products based on the conventional techniqueand then producing a W/O/W type composite emulsion by dispersing the W/Otype emulsion in an aqueous phase thereof with a water-solublemacromolecule provide a W/O/W type composite emulsion which has anextremely small particle diameter and sufficient stability and canpreserve the percent inclusion of medical substances included in aninternal aqueous phase at a high level. The present invention has beenaccomplished based on those findings.

Thus, the present invention provides a W/O/W type composite emulsion,wherein a W/O type emulsion comprising water, an oil ingredient and alipophilic emulsifier each in a proportion expressed in term of massratio falling within a range enclosed with bold lines in FIG. 1 isdispersed in an external aqueous phase with a water-solublemacromolecule blended therein.

According to the present invention, there is provided a W/O/W typecomposite emulsion with an average particle diameter in a range, withinwhich the dispersing stability in a liquid formulation can be preservedeasily, of 2000 nm or below, by providing a W/O type emulsion producedas described above while incorporating water, an oil ingredient and alipophilic emulsifier each in a specific proportion and dispersing theW/O type emulsion in an external aqueous phase with a water-solublemacromolecule, which W/O/W type composite emulsion can preserve thepercent inclusion of the medical substances included in the internalaqueous phase at a high level. In addition, the W/O/W type compositeemulsion according to the present invention can make the volume of aninternal aqueous phase larger, which enables in turn to drasticallyincrease the quantity of medical substances included in each particle ofthe W/O/W type composite emulsion.

As the lipophilic emulsifier used in the present invention, polyglycerinfatty acid ester having an HLB value of 10 or less is preferable.

In the case described above where polyglycerin fatty acid ester is usedas the lipophilic emulsifier, the polymerization degree of thepolyglycerin potion is preferably within the range of from 4 to 12.Preferably, the fatty acid portion of the polyglycerin fatty acid esteris an unsaturated fatty acid, more preferably, unsaturated fatty acidhaving 16 to 22 carbon atoms, and still more preferably, ahydroxy-unsaturated fatty acid. Specifically, oleic acid, linoleic acid,linolenic acid, ricinoleic acid and erucic acid are preferable andricinoleic acid is particularly preferable.

Those especially preferable polyglycerin-condensed ricinoleic acidesters include tetraglycerin-condensed ricinoleic acid ester,hexaglycerin-condensed ricinoleic acid ester, pentaglycerin-condensedricinoleic acid ester, decaglycerin-condensed ricinoleic acid ester andthe like as well as the mixtures thereof.

Oil ingredients used in the present invention include commonly-used onessuch as liquid paraffin, squalane, squalene, tocopherol, tocopherolacetate, tocopherol nicotinate, avocado oil, camellia oil, turtle oil,macadamia nuts oil, corn oil, mink oil, olive oil, rapeseed oil, yolkoil, sesame oil, wheat germ oil, Camellia sasanqua oil, castor oil,safflower oil, cottonseed oil, soybean oil, peanut oil and tricaprilyn,and of these tocopherol acetate is preferable. In addition, fat-solublemedical substances may be blended in the oil ingredients.

The preferable water-soluble macromolecules used in the presentinvention include water-soluble proteins, water-soluble syntheticpolymers, water-soluble polysaccharides and the derivatives thereof.

The water-soluble proteins include casein, sodium caseinate,β-lactoglobulin, α-lactalbumin, albumin, gelatin, soybean protein, andof these casein, sodium caseinate, β-lactoglobulin and α-lactalbumin arepreferable.

The water-soluble synthetic polymers include polyvinyl alcohol,polyvinyl pyrrolidone, carboxyvinyl polymer, polyvinyl methyl ether andpoly(sodium acrylate), and of these polyvinyl alcohol and polyvinylpyrrolidone are preferable.

The water-soluble polysaccharides or the derivatives thereof includexanthan gum, gelan gum, dextran, pullulan, gum arabic, carrageenan,locust bean gum, dextrin, guar gum, pectin, sodium alginate,hydroxypropylcellulose, hydroxypropyl methylcellulose, methylcellulose,hydroxyethylcellulose and carboxylmethylcellulose, and of these xanthangum and hydroxypropylcellulose are preferable.

The water-soluble macromolecules can be used in combination of two ormore.

The blend proportion of the water-soluble macromolecule according to thepresent invention preferably ranges from 0.001 to 20% by mass, and morepreferably from 0.01 to 10% by mass, of the external aqueous phase.

When the blend proportion of the water-soluble macromolecule is toosmall, it is difficult to produce a homogeneous and fine W/O/W typecomposite emulsion, while the blend proportion of the water-solublemacromolecule is too large, the resultant W/O/W type composite emulsionhas an undesirably high viscosity for internal application.

When medical substances having unpleasant taste or easily reacting withother components are blended in the internal aqueous phase of the W/O/Wtype composite emulsion according to the present invention, theadvantage of the present invention is fully exhibited, but even whencommonly-used water-soluble medical substances are blended therein, theadvantage can be expected in improvement of the stability.

The blend proportion of the water-soluble macromoleculemedicalsubstances that can be blended in the internal aqueous phase variesdepending upon the solubility, but the advantages of the presentinvention can be achieved by adjusting the blend proportions of the oilingredient and lipophilic emulsifier taking into considerations thequantity of internal aqueous phase after the medical substances havebeen dissolved therein so as to meet the presently recited blendproportion of each of the components.

In the present invention, commercial value of the product can beimproved by optionally blending pharmaceutical agents, other components,taste or odor reforming agents, pH adjusting agents, preservatives andthe like in the external aqueous phase so far as the effect of thepresent invention is not adversely affected.

The W/O/W type composite emulsion according to the present invention canbe produced as described below. At first, an oil phase such as an oilingredient and lipophilic emulsifier is put into a container. Thecontainer is set on an agitator such as a vacuum emulsifying machine.Then the mixture is heated while agitating to a temperature in theapproximate range of from 50 to 90° C., dissolved and homogenized. Thento the resultant mixture is added gradually a specified quantity of anaqueous phase containing substances and optional additives to beincluded in the internal aqueous phase, and the resultant mixture isemulsified while agitating the same at a constant temperature in theapproximate range of from 50 to 90° C. Thereafter, the resultantemulsion is cooled to 20 to 40° C. while agitating for a certain periodof time to obtain a W/O type emulsion. At this point of time, it ispreferable that the W/O type emulsion is formed so as to have an averageparticle diameter of from approximately 10 to 500 nm. The W/O/W typecomposite emulsion can be produced by further dispersing this W/O typeemulsion in an external aqueous phase containing a specified quantity ofa water-soluble macromolecule and optional additives with any of theordinary methods such as high-pressure homogenizer method, high-speedagitating method, ultrasonic wave emulsifying method and membraneemulsifying method. In addition, heating may be performed, if necessary,in the step of preparing the W/O/W type composite emulsion.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention is further described in detail with reference toExamples and Test Examples.

Example 1 Preparation of W/O Type Emulsion

a: Internal aqueous phase Ferric ammonium citrate  8.5 g Water 76.5 g b:Oil ingredient Tocopherol acetate 37.5 g c: Lipophilic emulsifierPolyglycerin-condensed 127.5 g  ricinoleic acid ester (produced bySakamoto Yakuhin Kogyo Co., Ltd., CRS-75)

Components b and c were heated to 70 to 80° C., and were homogeneouslymixed and dissolved. Then the component a was gradually added to theresultant mixture while agitating. The mixture was agitated andemulsified while maintaining the liquid temperature at approximately 70to 80° C. The resultant emulsion was further agitated for a certainperiod of time while gradually cooling it to a temperature of from 20 to40° C. to obtain a W/O type emulsion.

The average particle diameter of the W/O type emulsion determined with agrain size distribution measuring device based on dynamic lightscattering system (NICOMP Model 370 (produced by HIAC/ROYCO)) was 113.8nm.

Preparation of W/O/W Type Composite Emulsion

20 g of the W/O type emulsion obtained as described above was added,while agitating it with a homogenizer, to 180 g of an aqueous solutioncontaining 0.5% by mass of sodium caseinate and 20% by mass of sugar, toobtain a W/O/W type composite emulsion with a relatively large particlediameter. Thereafter, the W/O/W type composite emulsion was passedthrough a perforated membrane to obtain a fine W/O/W type compositeemulsion with an average particle diameter of 799.6 nm. The averageparticle diameter of the W/O/W type composite emulsion was determinedwith a grain size distribution measuring device based on laser beamdiffraction/scattering system (HORIBA LA-920).

Measurement of Percent Inclusion of Medical Substances

The percent inclusion of the substances included in the W/O/W typecomposite emulsion was calculated through the following equation:

Percent inclusion (%)=(Wi−Wo×A)/Wi×100 wherein Wi is a mass ofsubstances included in the W/O/W type composite emulsion; Wo is a massof substances included in the external aqueous phase; and A is aquotient of the mass of external aqueous phase by the mass of W/O/W typecomposite emulsion ((mass of external aqueous phase)/(mass of W/O/W typecomposite emulsion)).

The mass of the substances included in the W/O/W type composite emulsionwas measured after preprocessing by means of wet cineration method,etc., whereas the mass of the substances included in the externalaqueous phase was measured after subjecting the W/O/W type compositeemulsion to centrifugation to separate the particles of the W/O/W typecomposite emulsion from the external aqueous phase, each with atomicabsorption method, respectively. As a result, it was found that thepercent inclusion of the included substances (the included substance wasiron in this case) was 98.29%.

Examples 2 to 8 Preparation of W/O Type Emulsion

Each of the samples was prepared with the composition shown in Table 1in the same production method as that employed in Example 1. The averageparticle diameter of the W/O type emulsion was also measured in the samemanner as that employed in Example 1.

In the table showing the results in the Examples, FAC indicates ferricammonium citrate, and PGCR indicates polyglycerin-condensed ricinoleicacid ester (produced by Sakamoto Kogyo Co., Ltd., CRS-75).

Preparation of W/O/W Type Composite Emulsion

The W/O/W type composite emulsion was prepared by the same productionmethod as that employed in Example 1. The average particle diameter ofthe W/O/W type composite emulsion was also measured in the same manneras that in Example 1.

Measurement of the Percent Inclusion of Included Substances

The percent inclusion of the substances (In this case, the includedsubstance was iron) in the W/O/W type composite emulsion was measured inthe same manner as that in Example 1.

TABLE 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6Example 7 Example 8 Composi- Purified water 76.50 76.50 76.50 76.5076.50 76.50 76.50 76.50 tion of FAC (g) 8.50 8.50 8.50 8.50 8.50 8.508.50 8.50 W/O type PGCR (g) 127.50 127.50 127.50 127.50 127.50 127.50127.50 127.50 emulsion Tocopherol 37.50 37.50 37.50 37.50 37.50 37.5037.50 37.50 acetate (g) Average particle diameter 113.8 113.8 113.8113.8 113.8 113.8 113.8 113.8 of W/O type emulsion (nm) Composi- W/Oemulsion 20 5 5 5 5 5 5 5 tion of (nm) W/O/W Sodium caseinate 0.9 — — —— — — — type (g) compos- Polyvinyl — 0.225 0.9 2.25 — — — 0.95 itealcohol (g) emulsion Polyvinyl — — — — 0.45 — — — pyrrolidone (g)Hydroxypropyl- — — — — — 0.225 — — cellulose (g) Xanthan gum (g) — — — —— — 0.0225 — Sugar (g) 36 9 9 9 9 9 9 19 Purified water 143.1 35.77535.1 33.75 35.5 35.775 35.9775 75.05 (g) Average particle diameter 799.6614.1 569.8 560.7 737.9 592.6 772.5 233.6 of W/O/W type compositeemulsion (nm): C Percent inclusion of 98.29 99.01 99.03 98.83 100.099.13 99.89 97.92 iron (%): B B/Log₁₀C 33.86 35.51 35.94 35.95 34.8735.75 34.59 41.34

As clearly shown in Table 1, when the W/O type emulsions having theblend proportions within the range according to the present inventionare dispersed in an external aqueous phase with a water-solublemacromolecule such as water-soluble protein, water-soluble syntheticpolymer or water-soluble polysaccharide, very fine W/O/W type compositeemulsions with a high percent inclusion of medical substances could beobtained. Further, the W/O/W type composite emulsions were very fine aswell as they met the requirement that the value obtained by dividing thepercent inclusion (%) of the medical substances dissolved in theinternal aqueous phase of the W/O/W type composite emulsion by thecommon logarithm for the average particle diameter of the W/O/W typecomposite emulsion (nm) (B/Log₁₀ C in Table 1) is 27 or more (SeeExamples 1 to 8).

Examples 9 to 15 and Comparative Examples 1 to 5 Preparation of W/O TypeEmulsion

Each of the samples was prepared with the composition shown in Table 2or 3 by the same production method as that employed in Example 1. Theaverage particle diameter of the W/O type emulsion was also measured inthe same manner as that employed in Example 1.

Preparation of W/O/W Type Composite Emulsion

10 g of the W/O type emulsion obtained as described above was added,while agitating with a magnetic stirrer or a homogenizer, to 90 g of anaqueous solution containing 2% by mass of polyvinyl alcohol and 20% bymass of sugar to obtain a first W/O/W type composite emulsion with arelatively large particle diameter. The first W/O/W type compositeemulsion was passed through a perforated membrane to obtain a fine W/O/Wtype composite emulsion. The average particle diameter of the fine W/O/Wtype composite emulsion was measured with a grain size distributionmeasurement device based on the laser diffraction/scattering system(HORIBA LA-920).

Measurement of the Percent Inclusion of Medical Substances

The percent inclusion of the included substances (the included substancewas iron in the Examples herein) in the fine W/O/W type compositeemulsion was measured in the same manner as that employed in Example 1.

TABLE 2 Example 9 Example 10 Example 11 Example 12 Example 13 Example 14Example 15 Composi- Purified water 45.00 58.50 76.50 90.00 90.00 76.5076.50 tion of FAC (g) 5.00 6.50 8.50 10.00 10.00 8.50 8.50 W/O type PGCR(g) 75.00 97.50 127.50 100.00 75.00 102.50 77.50 emulsion Tocopherol125.00 87.50 37.50 50.00 75.00 62.50 87.50 acetate (g) Average particlediameter 203.3 162.1 113.8 147.6 182.4 140.0 204.0 of W/O type emulsion(nm) Composi- W/O emulsion 10 10 10 10 10 10 10 tion of (nm) W/O/WPolyvinyl 1.8 1.8 1.8 1.8 1.8 1.8 1.8 type alcohol (g) composite Sugar(g) 18 18 18 18 18 18 18 emulsion Purified water 70.2 70.2 70.2 70.270.2 70.2 70.2 (g) Average particle diameter 420.5 452.2 556.0 563.3489.6 494.7 456.4 of W/O/W type composite emulsion (nm): C Percentinclusion of 91.94 99.67 99.65 99.32 92.65 99.50 89.19 iron (%): BB/Log₁₀C 35.04 37.54 36.30 36.11 34.44 36.93 33.54

TABLE 3 Comparative Comparative Comparative Comparative ComparativeExample 1 Example 2 Example 3 Example 4 Example 5 Composi- Purifiedwater 27.00 75.00 70.62 64.42 45.00 tion of FAC (g) 3.00 8.33 7.85 7.165.00 W/O type PGCR (g) 45.00 41.67 6.54 13.42 50.00 emulsion Tocopherol175.00 125.00 15.00 15.00 0.00 acetate (g) Average particle diameter190.5 189.8 Not Not Not of W/O type emulsion (nm) produced producedproduced Composi- W/O emulsion 10 10 — — — tion of (nm) W/O/W Polyvinyl1.8 1.8 — — — type alcohol (g) composite Sugar (g) 18 18 — — — emulsionPurified water 70.2 70.2 — — — (g) Average particle diameter 364.7 425.5— — — of W/O/W type composite emulsion (nm): C Percent inclusion of57.34 61.24 — — — iron (%): B B/Log₁₀C 22.38 23.29 — — —

As described above, when the W/O type emulsion having blend proportionswithin the range according to the present invention is dispersed in anexternal aqueous phase with a water-soluble macromolecule, a very fineW/O/W type composite emulsions with a high percent inclusion of medicalsubstances could be obtained. Further, the W/O/W type compositeemulsions were very fine as well as they met the requirement that thevalue obtained by dividing the percent inclusion (%) of the medicalsubstances dissolved in the internal aqueous phase of the W/O/W typecomposite emulsion by the common logarithm for the average particlediameter of the W/O/W type composite emulsion (nm) (B/Log₁₀ C inTable 1) is 27 or more (See Examples 9 to 15). To the contrary, when thecomposition of the W/O type emulsion was outside the range according tothe present invention, any W/O/W type composite emulsion with excellentcharacteristics could not be obtained (See Comparative examples 1 to 5).

INDUSTRIAL APPLICABILITY

With the present invention, it has become possible to blend medicalsubstances each with unfavorable taste or unstable medical substanceseven in a liquid solution of low viscosity.

Because of the characteristics, now even the medical substances, whichhave hardly been blended in a liquid formulation for internalapplication, an injection or the like, can be used for production ofmedical drugs.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a view showing the range of composition, in which theadvantages of the invention can be obtained, plotted with the blendproportion of the lipophilic emulsifier along the bottom edge, that ofthe water along the left sloped edge, and that of the oil ingredientalong the right sloped edges, respectively.

1. A W/O/W type composite emulsion, wherein a W/O type emulsioncomprising water, an oil ingredient and a lipophilic emulsifier each ina proportion expressed in term of mass ratio falling within a rangeenclosed with bold lines in FIG. 1 is dispersed in an external aqueousphase with a water-soluble macromolecule blended therein, wherein theexternal aqueous phase with the water-soluble macromolecule blendedtherein comprises from 0.001 to 20% by mass of the water-solublemacromolecule, and wherein the lipophilic emulsifier is a polyglycerinunsaturated fatty acid ester having an HLB value of 10 or below.
 2. TheW/O/W type composite emulsion according to claim 1, wherein the emulsionhas an average particle diameter falling within the range of from 20 to2000 nm.
 3. The W/O/W type composite emulsion according to claim 1,wherein the polyglycerin unsaturated fatty acid ester is apolyglycerin-condensated ricinoleic acid ester.
 4. The W/O/W typecomposite emulsion according to claim 1, wherein the water-solublemacromolecule is one or more members selected from the group consistingof water-soluble proteins, water-soluble synthetic polymers,water-soluble polysaccharides and derivatives thereof.
 5. The W/O/W typecomposite emulsion according to claim 1, wherein the water-solublemacromolecule is a water-soluble protein.
 6. The W/O/W type compositeemulsion according to claim 5, wherein the water-soluble protein iscasein, sodium caseinate, β-lactoglobulin or α-lactoalubumin.
 7. TheW/O/W type composite emulsion according to claim 1, wherein thewater-soluble macromolecule is a water-soluble synthetic polymer.
 8. TheW/O/W type composite emulsion according to claim 7, wherein thewater-soluble synthetic polymer is polyvinyl alcohol or polyvinylpyrrolidone.
 9. The W/O/W type composite emulsion according to claim 1,wherein the water-soluble macromolecule is polysaccharide or aderivative thereof.
 10. The W/O/W type composite emulsion according toclaim 9, wherein the water-soluble polysaccharide or a derivativethereof is xanthan gum or hydroxy propylcellulose.
 11. The W/O/W typecomposite emulsion according to claim 1, wherein the emulsion has avalue obtained by dividing a percent inclusion (%) of a medicalsubstances dissolved in an internal aqueous phase of the W/O/W typecomposite emulsion by a common logarithm for an average particlediameter (nm) of the W/O/W type composite emulsion of 27 or more. 12.The W/O/W type composite emulsion according to claim 1, wherein theemulsion has a viscosity of 150 mPa·s or below.
 13. The W/O/W typecomposite emulsion according to claim 1, wherein the emulsion is aliquid formulation for internal application.
 14. The W/O/W typecomposite emulsion according to claim 7, wherein the water-solublesynthetic polymer is polyvinyl alcohol.